The principal objective of this work is to exploit the special peculiarities of the feline hemoglobin and erythrocyte systems for investigating problems related to: a) the structure, function and regulation of the hemoglobins; b) the genetics and molecular control mechanisms in the biosynthesis of hemoglobins; and c) the control of 2,3-DPG metabolism. Understanding of the basis for the unusual properties of the feline hemoglobins, including their oxygen equilibria, tetramer-dimer dissociation and response to 2,3-DPG, will be sought by obtaining more information on their primary structures. The properties of the proteins will be examined in a number of ways to probe structure-function relationships, HbA and HbB, to functional regulation by organic phosphates. The low steady state levels of 2,3-DPG and ATP in normal cats, and their sharp rise with drug-induced anemia will serve as primary models to examine glycolytic control mechanism(s). Another aspect of this research is to ascertain the genetic mechanism that accounts for the production of variable proportions of the 2,3-DPG sensitive and insensitive HbA to HbB in different cats. Reticulocyte lysates from animals of the 1/1, 2/1, and 10/1 HbA/HbB phenotypes will be separated into components to determine the factor(s) that control the quantitative production of the two proteins. Hemoglobin synthesis will be measured in reconstituted lysates by following the rates of incorporation of labeled amino acids into the proteins.